A 3-month-old infant referred from newborn hearing screening shows bilateral symmetric sensorineural hearing loss of 85 dB across all frequencies on diagnostic ABR. Imaging (MRI temporal bones) is normal—no cochlear malformations, no enlarged vestibular aqueduct, no nerve aplasia. The audiologic pattern marked **A** in the diagram is consistent with connexin-26 (GJB2) mutation. Which of the following best explains the pathophysiology of hearing loss in this condition?
A. Stapes footplate fixation preventing transmission of sound vibrations to the inner ear
B. Accumulation of endolymph in the cochlear duct due to abnormal aquaporin-2 expression
C. Failure of potassium recycling from the cochlea due to disrupted gap junction function in supporting cells and fibrocytes
D. Degeneration of spiral ganglion neurons secondary to viral infection during fetal development
Explanation
Why "Failure of potassium recycling from the cochlea due to disrupted gap junction function in supporting cells and fibrocytes" is right
Connexin-26 (GJB2) encodes a gap junction protein essential for potassium (K+) recycling in the cochlea. During hair cell transduction, K+ is released into the endolymph; it must be recycled back to the stria vascularis through gap junctions in supporting cells and fibrocytes to maintain the endocochlear potential. Mutations in GJB2 disrupt this recycling pathway, causing failure of endocochlear potential maintenance and subsequent outer hair cell death. This mechanism directly explains the bilateral, symmetric, severe-to-profound sensorineural hearing loss seen in connexin-26-related deafness (DFNB1). The normal imaging findings (no cochlear malformations, no nerve aplasia) rule out structural etiologies and support a functional/metabolic defect—precisely what connexin-26 dysfunction represents (Cummings Otolaryngology 7e).
Why each distractor is wrong
Stapes footplate fixation preventing transmission of sound vibrations to the inner ear: This describes otosclerosis (option B in the diagram), which causes conductive or mixed hearing loss with normal bone conduction thresholds initially. The patient has pure sensorineural loss with normal imaging, ruling out stapes fixation.
Accumulation of endolymph in the cochlear duct due to abnormal aquaporin-2 expression: This mechanism is associated with enlarged vestibular aqueduct (EVA) and Pendred syndrome (SLC26A4 mutations), not GJB2. The patient's MRI explicitly shows no EVA, and Pendred syndrome is syndromic (thyroid involvement), whereas connexin-26 deafness is non-syndromic.
Degeneration of spiral ganglion neurons secondary to viral infection during fetal development: Viral infection (e.g., CMV, rubella) causes congenital hearing loss but is not genetic and would not be confirmed by GJB2 sequencing. Connexin-26 mutations cause primary cochlear dysfunction, not secondary neuronal degeneration from infection.
High-YieldNEET PG
Connexin-26 (GJB2) mutations account for ~50% of severe-to-profound prelingual genetic deafness; the pathophysiology is failure of K+ recycling via gap junctions, not structural malformation or infection.
